| 1. |
- Adlercreutz, Emma, et al.
(författare)
-
A gluten free diet lowers NKG2D and ligand expression in BALB/c and NOD mice.
- 2014
-
Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 177:2, s. 391-403
-
Tidskriftsartikel (refereegranskat)abstract
- The interplay between diet and immune-parameters which could affect type 1 diabetes (T1D) pathogenesis is not sufficiently clarified. Intestinal upregulation of the activating receptor NKG2D(CD314) and its ligands is a hallmark of celiac disease (CD). However, the direct effect of gluten on NKG2D expression is not known. We studied, by FACS (lymphoid tissues) and RT-qPCR (intestine and pancreatic islets), if a gluten-free diet from 4 weeks (GF diet) or a gluten-free diet introduced in breeding pairs (SGF diet), induces changes in NKG2D expression on NK-cells DX5(+) (CD49b) and CD8(+) T-cells, as well as in intestinal and islet levels of NKG2D and ligands in BALB/c and NOD mice. Gluten-free NOD mice had lower insulitis (p<0.0001). Gluten-free NOD mice had reduced expression of NKG2D on DX5(+) NK-cells in spleen and auricular lymph nodes (p<0.05) and on CD8(+) T-cells in pancreas associated lymph nodes (p=0.04). Moreover, the level of CD71 on DX5(+) NK-cells and CD8(+) T-cells (p<0.005) was markedly reduced. GF and SGF mice had reduced expression of NKG2D and DX5 mRNA in intestine (p<0.05). Differences in intestinal mRNA expression were found in mice of 8, 13 and 20 weeks. Intestinal expression of NKG2D ligands was reduced in SGF mice with lower expression of all ligands. In isolated islets, a SGF diet induced a higher expression of specific NKG2D ligands. Our data shows that a gluten-free diet reduces the level of NKG2D and the expression of NKG2D ligands. These immunological changes may contribute to the lower T1D incidence associated with a gluten-free diet.
|
|
| 2. |
- Björck, Sara, et al.
(författare)
-
Screening Detects a High Proportion of Celiac Disease in Young HLA-genotyped Children.
- 2010
-
Ingår i: Journal of Pediatric Gastroenterology and Nutrition - Jpgn. - 1536-4801. ; 50, s. 49-53
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS:: Celiac disease is associated with tissue transglutaminase autoantibodies (tTGAb) and the human leukocyte antigen (HLA)-risk alleles DQB1*02 and DQB1*0302. The aim was to estimate the proportion of undiagnosed celiac disease in children with HLA risk at 3 years of age. PATIENTS AND METHODS:: From a population-based HLA-DQ screening study of newborns born between June 2001 and August 2004 in the southern part of Sweden, 6206 children with HLA-risk alleles were identified and asked to participate at a mean 3.3 +/- 0.4 years of age. As controls, 7654 children with HLA-nonrisk alleles were asked to participate. In all, 1620 (26.1%) children with HLA risk and 1815 (23.7%) controls were screened for tTGAb using radioligand-binding assays. Celiac disease was established by intestinal biopsy in children with a confirmed positive tTGAb test. RESULTS:: Twenty-three children reported already having clinically diagnosed celiac disease and did not participate further. In children with HLA-risk genotypes, 73 of 1620 (4.5%, 95% CI 3.5%-5.5%) were tTGAb-positive compared with none of 1815 from the controls (P < 0.0001). Seventy-one children underwent biopsy (1 refused biopsy and 1 biopsy failed), of whom 56 of 1618 (3.5%, 95% CI 2.6%-4.4%) had damaged intestinal mucosa classified as celiac disease. The ratio between clinically and screening detected celiac disease in this study was 1:2.4 (23:56). CONCLUSIONS:: The proportion of clinically undetected celiac disease may be particularly high among 3-year-old children with HLA-DQB1*02 and DQB1*0302 in Sweden, where these 2 HLA-risk alleles frequently occur.
|
|
| 3. |
- Browaldh, Lars, et al.
(författare)
-
Celiaki är en vanlig sjukdom som är lätt att missa
- 2014
-
Ingår i: Läkartidningen. - : Swedish Medical Association. - 0023-7205 .- 1652-7518. ; 111:11, s. 484-488
-
Tidskriftsartikel (refereegranskat)abstract
- Celiaki ansågs länge som en ovanlig barnsjukdom, men är en vanlig sjukdom som drabbar alla åldrar. Genomförda screeningar av normalbefolkningen visar att merparten inte fått diagnos eller behandling. Den kliniska bilden varierar: alltifrån diffusa besvär eller inga symtom alls till allvarliga gastrointestinala symtom med grav avmagring och tillväxtrubbning till följd av malabsorption. Klinisk misstanke om eller hereditet för celiaki bör föranleda analys av specifika serologiska markörer. Gastroskopi med tunntarmsbiopsi bör övervägas för att bekräfta eller utesluta diagnosen.
|
|
| 4. |
- Danielsson, Anna-Karin, et al.
(författare)
-
Cannabis use in adolescence and risk of future disability pension : A 39-year longitudinal cohort study
- 2014
-
Ingår i: Drug And Alcohol Dependence. - : Elsevier BV. - 0376-8716 .- 1879-0046. ; 143, s. 239-243
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: This study aimed at examining a possible association between cannabis use in adolescence and future disability pension (DP). DP can be granted to any person in Sweden aged 16-65 years if working capacity is judged to be permanently reduced due to long-standing illness or injury. Methods: Data were obtained from a longitudinal cohort study comprising 49,321 Swedish men born in 1949-1951 who were conscripted to compulsory military service aged 18-20 years. Data on DP was collected from national registers. Results: Results showed that individuals who used cannabis in adolescence had considerably higher rates of disability pension throughout the follow-up until 59 years of age. In Cox proportional-hazards regression analyses, adjustment for covariates (social background, mental health, physical fitness, risky alcohol use, tobacco smoking and illicit drug use) attenuated the associations. However, when all covariates where entered simultaneously, about a 30% increased hazard ratio of DP from 40 to 59 years of age still remained in the group reporting cannabis use more than 50 times. Conclusions: This study shows that heavy cannabis use in late adolescence was associated with an increased relative risk of labor market exclusion through disability pension.
|
|
| 5. |
|
|
| 6. |
- Kjellerås, Jennifer, et al.
(författare)
-
Improved efficacy by using the pTnT-rhtTG plasmid for the detection of celiac disease specific tissue transglutaminase autoantibodies in radioligand binding assays
- 2011
-
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa Healthcare. - 0036-5513 .- 1502-7686. ; 71:8, s. 701-704
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Tissue transglutaminase (tTG) autoantibodies are serological markers for celiac disease. The aim was to study the efficacy of the pTnT-rhtTG plasmid and subsequent diagnostic accuracy of tTG autoantibodies for childhood celiac disease using radioligand binding assays.Methods: Coupled in vitro transcription and translation of tTG were performed by pTnT-rhtTG as well as by the pGEMt Easy-rhtTG vectors using the TNT SP6 Coupled Reticulocyte Lysate System in the presence of [(35)S] methionine. Sera from 190 celiac disease children and 74 controls were measured for tTG autoantibodies in two separate radioligand binding assays using anti-human IgA agarose and protein A sepharose beads for the detection of IgA-tTG and IgG-tTG, respectively.Results: Median incorporation of [(35)S] methionine into the pTnT-rhtTG was 26% compared to 16% for the pGEMt Easy-rhtTG plasmid (p = 0.0016). Using pTnT-rhtTG (as compared to pGEMt Easy-rhtTG), sensitivities were IgA-tTG = 96.3% (95.7%) and IgG-tTG = 95.8% (97.3%) and specificities were IgA-tTG = 91.9% (90.5%) and IgG-tTG = 94.6% (98.4%). According to receiver operator characteristics for the pTnT (pGEMt Easy) assays, area under the curves were IgA-tTG = 98.4% (98.4%) and IgG-tTG = 97.7% (97.2%), respectively.Conclusion: The pTnT-rhtTG plasmid increased the efficacy of tTG antigen usage without reducing the diagnostic accuracy of IgA-tTG and IgG-tTG for childhood celiac disease. The pTnT-rhtTG plasmid is therefore recommended over the pGEMt Easy-rhtTG for the assessment of IgA-tTG and IgG-tTG using radioligand binding assays.
|
|
| 7. |
- Kjellerås, Jennifer, et al.
(författare)
-
Improved efficacy by using the pTnT-rhtTG plasmid for the detection of celiac disease specific tissue transglutaminase autoantibodies in radioligand binding assays.
- 2011
-
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 71, s. 701-704
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Tissue transglutaminase (tTG) autoantibodies are serological markers for celiac disease. The aim was to study the efficacy of the pTnT-rhtTG plasmid and subsequent diagnostic accuracy of tTG autoantibodies for childhood celiac disease using radioligand binding assays. Methods. Coupled in vitro transcription and translation of tTG were performed by pTnT-rhtTG as well as by the pGEMt Easy-rhtTG vectors using the TNT SP6 Coupled Reticulocyte Lysate System in the presence of [(35)S] methionine. Sera from 190 celiac disease children and 74 controls were measured for tTG autoantibodies in two separate radioligand binding assays using anti-human IgA agarose and protein A sepharose beads for the detection of IgA-tTG and IgG-tTG, respectively. Results. Median incorporation of [(35)S] methionine into the pTnT-rhtTG was 26% compared to 16% for the pGEMt Easy-rhtTG plasmid (p = 0.0016). Using pTnT-rhtTG (as compared to pGEMt Easy-rhtTG), sensitivities were IgA-tTG = 96.3% (95.7%) and IgG-tTG = 95.8% (97.3%) and specificities were IgA-tTG = 91.9% (90.5%) and IgG-tTG = 94.6% (98.4%). According to receiver operator characteristics for the pTnT (pGEMt Easy) assays, area under the curves were IgA-tTG = 98.4% (98.4%) and IgG-tTG = 97.7% (97.2%), respectively. Conclusion. The pTnT-rhtTG plasmid increased the efficacy of tTG antigen usage without reducing the diagnostic accuracy of IgA-tTG and IgG-tTG for childhood celiac disease. The pTnT-rhtTG plasmid is therefore recommended over the pGEMt Easy-rhtTG for the assessment of IgA-tTG and IgG-tTG using radioligand binding assays.
|
|
| 8. |
- Lavant, Eva, et al.
(författare)
-
A new PCR-SSP method for HLA DR-DQ risk assessment for celiac disease
- 2011
-
Ingår i: Clinica Chimica Acta. - : Elsevier. - 0009-8981 .- 1873-3492. ; 412:9-10, s. 782-784
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Susceptibility to celiac disease is essentially restricted to carriers of specific HLA DQA1 and DQB1 alleles. We have developed a semi-automated sequence specific primer (SSP) PCR method for clinical HLA typing and compared the test results with those from a commercial method. Methods: Primers for each DQA1 and DQB1 allele group were included in our PCR-SSP reaction to allow differentiation of homozygous from heterozygous carriers of risk alleles. Primers detecting the tightly linked DRB1*04, *03, *07 and *09 alleles were included to resolve potentially ambiguous results. Fluorescently labeled PCR products of 119 clinical samples were analyzed by capillary electrophoresis, and results were compared to those previously obtained from the DELFIA® Type 1 Diabetes Genetic Predisposition assay. Results: The risk assessment derived from the two methods was 100% concordant. One previously unreported haplotype was detected and haplotype assignments in two of the 119 samples were improved from previous reports. Conclusions: The use of three PCR reactions and a single electrophoretic step for DQA1, DQB1 and DRB1 typing provides distinction of celiac disease associated alleles and their homo- or heterozygous status. This multiplex analysis reduces reagent costs, personnel and instrument time, while enabling improved allelic assignment through HLA-DR-DQ haplotype association.
|
|
| 9. |
- Lindehammer, Sabina, et al.
(författare)
-
Early human pregnancy serum cytokine levels predict autoimmunity in offspring.
- 2011
-
Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 44, s. 445-452
-
Tidskriftsartikel (refereegranskat)abstract
- It is generally believed that pregnancy is mediated by a Th2 response, which includes cytokines that promote placental growth and are involved in inducing tolerance to the foetus. If the balance between Th1/and Th2-mediated cytokines is disrupted, systemic and local changes could predispose the foetus to future disease. Therefore, a shift in the Th1/Th2 balance during pregnancy, possibly caused by underlying environmental factors, could be associated with post-partum autoimmune disease in the offspring. Based on this presumption, we used celiac disease as a model to investigate whether autoimmunity is triggered in the foetus during early pregnancy, observed as changes in the mother's cytokine profile. Ten cytokines were measured by electro-chemi-luminescent multiplex ELISA in serum samples obtained from mothers during early pregnancy. Cases included women with children who had developed verified celiac disease before the age of 5, who were compared with other women as matched controls. We observed that 7 out of 10 cytokine levels were significantly increased in our case mothers when compared to controls. Five of these belonged to what is generally known as a Th1-mediated response (TNF?, IFN?, IL-2, IL-1? and IL-12) and two were Th2 cytokines (IL-13 and IL-10). However, the IL-10 cytokine is known to have features from both arms of the immune system. These results were confirmed in a logistic regression model where five out of the initial seven cytokines remained. This study suggests that increase in Th1 serum cytokines may be associated with celiac disease in offspring.
|
|
| 10. |
|
|
